Technique for greatly shortening the transition from methadone to naltrexone maintenance of patients addicted to opiates.

Acute methadone detoxification was induced by the intravenous administration of naloxone during simultaneous intravenous sedation with midazolam, a fully reversible short-acting benzodiazepine, in seven patients addicted to opiates. Within hours the patients tolerated full doses of naltrexone. This technique enables patients to transfer easily, quickly, and safely from methadone to naltrexone maintenance.

Psychophysiological reactions in methadone maintenance patients do not correlate with methadone plasma levels.

In methadone maintenance therapy methadone plasma concentrations of 400 ng/ml are necessary to suppress any further opiate action and to provide stabilized maintenance. In a controlled study we have searched for a differentiation in autonomous activation between patients having low and high methadone plasma levels, using static and dynamic pupillometry and habituation of skin conductance response. Results show that there is no difference in psychophysiological response between patients with high (greater than 400 ng/ml) or low (less than 400 ng/ml) plasma levels of methadone. This indicates that there is no reduction in behavioral arousal in patients with high plasma methadone levels. On the basis of these findings, there is no rationale to maintain patients on plasma levels below 400 ng/ml.

Continuous naloxone administration suppresses opiate withdrawal symptoms in human opiate addicts during detoxification treatment.

In a small clinical trial, a new therapeutic approach was studied, whether naloxone, in high dosage over a prolonged period of time, will attenuate withdrawal symptoms in acute opiate detoxification. Six opiate addicts, satisfying DSM III-R criteria of opiate dependence, were given 10 mg naloxone under short barbiturate anaesthesia, followed by repeated doses of 0.4 mg/h naloxone for at least 72 h. Acute onset of withdrawal symptoms brought about a high dose of naloxone could be suppressed by the short barbiturate anaesthetic; neither continuous supply nor cessation of the naloxone regimen after 96 h caused any severe withdrawal symptoms. Morphine and naloxone measurements in blood at the start of naloxone therapy enabled pharmacokinetic explanations for this paradoxical action of naloxone to be excluded.

Treatment of severe mania with intravenous magnesium sulphate as a supplementary therapy.

Ten patients with severe, therapy-resistant manic agitation received magnesium sulphate infusions with a continuous magnesium (Mg) flow of approximately 200 mg/h (4353+/-836 mg/day; daily monitored Mg plasma level: 2.44+/-0.34 mmol/l) for periods ranging from 7 to 23 days. Concomitant psychotropic treatment consisted of lithium (n = 10), haloperidol (n = 5) and clonazepam (n = 10). During i.v. Mg treatment the mean values of the maximum dosages of neuroleptics (in chlorpromazine equivalents) and benzodiazepines (in diazepam equivalents) were significantly lower than during the last day of pretreatment (= baseline). Seven patients showed a marked improvement in the Clinical Global Impression scale. In case of bradycardia detected by the ECG monitor (n = 5), Mg flow was reduced and bradycardia disappeared promptly. Mg i.v. may be a useful supplementary therapy for the clinical management of severe manic agitation. This open study needs double-blind confirmation.

Combined naloxone/methadone preparations for opiate substitution therapy.

Every opportunity should be used to reduce the risk of HIV-1 infection and transmission among intravenous drug users (IVDUs). Methadone maintenance is widely accepted to keep the drug user away from risk-laden practices and to stop intravenous drug use. In order to minimize the diversion and intravenous abuse of methadone in maintenance programs, the effects of a combined naloxone/methadone preparation through oral intake and the effects of an intravenous administration were tested. In opiate addicts, the intravenous administration of this mixture caused a severe withdrawal syndrome lasting for 15 to 30 minutes. The oral administration of this combination was indistinguishable from methadone alone. It is argued that this combination therapy prevents the intravenous abuse of methadone in maintenance programs.

Psychophysiological research in psychiatry and neuropsychopharmacology. I. Methodological aspects of the Viennese Psychophysiological Test-System (VPTS).

In order to find a psychophysiological paradigm for clinical application we have developed the Viennese Psychophysiological Test-System (VPTS), which includes a special selection and combination of experimental situations, physiological measurements, behavioral measurements and data analysis. This study presents detailed information concerning these four aspects. Experimental situations are related to the human model of information processing, where short changes of stimulus-reaction-correlated processes are selected: resting conditions (eyes open, eyes closed), habituation-orienting test, psychomotor-performance test, signal-detection test and reaction-time test. Physiological measures include central and peripheral activity of the cerebrospinal and autonomic nervous system: cortical activity (spontaneous electroencephalogram, auditory evoked potentials, late positive components, slow potentials), ocular activity (eye and eyelid movements), electrodermal activity (skin conductance), cardiac activity (heart rate measurement), respiratory activity (rate of respiration) and peripheral vascular activity (finger pulse volume). Behavioral measurements extend from micro behavior to complex diagnostic systems: psychomotor measurements, self-reported mood, arousal and visceral perception, psychological and psychiatric interviews. The application of this test system in 15 elderly subjects of both sexes aged 58-77 years gives information which exceeds the sum of the singular constructing elements of the VPTS.

Psychophysiological research in psychiatry and neuropsychopharmacology. II. The investigation of antihypoxidotic/nootropic drugs (tenilsetam and co-dergocrine-mesylate) in elderlies with the Viennese Psychophysiological Test-System (VPTS).

In a double-blind placebo-controlled study, the effects of tenilsetam, a novel antihypoxidotic/nootropic agent, on spontaneous and event-related activity of the central and autonomous nervous system were studied in 15 elderly subjects of both sexes aged 58-77 years by means of the Viennese Psychophysiological Test-System (VPTS). The VPTS includes a special selection and combination of experimental situations, physiological measurements, behavioral measurements and data analysis. At weekly intervals, the subjects received randomized single oral doses of placebo, 150 mg, 300 mg and 900 mg tenilsetam (TEN) and 5 mg co-dergocrine-mesylate (CDM) as reference drug. Psychophysiological testings were carried out before and 2 h after drug administration. Evaluation of the spontaneous EEG-activity demonstrated no significant drug effects as compared to placebo. In contrast, TEN showed a dose-dependent augmentation of the N1-P2 and N2-P300 amplitudes of the event-related potentials (ERPs) in specific experimental conditions. In reference to placebo, the increase of N2-P300 amplitude after the highest dosage of TEN, as well as after CDM, amounted to approximately 5 microV, which confirms the hypothesis that nootropic drugs may influence the P300 amplitude in the sense of an improved availability of cognitive processing resources. There was no effect on ERP latencies, on mean amplitudes of contingent negative variation and of post-imperative negative variation, on autonomous nervous system, on psychological measurements, nor on reaction time. However, specific improvements were observed in psychomotor measures, such as synchronization accuracy and rhythmicity. These findings highlight the importance of using EEG and ERP measures in different experimental situations in conjunction with behavioral, psychological and autonomous nervous system measures to study nootropic drug effects.

[Clonidine for the treatment of heroin withdrawal syndrome]. / Clonidin zur Behandlung des Heroinentzugssyndroms.

In an open study of 50 patients with heroin addiction, clonidine was efficacious by mouth in the treatment of acute heroin-withdrawal syndrome. Mean administration of clonidine (on an "as-needed" basis) was 5 days (maximum 7 days), whilst the mean daily dosage ranged from 0.112 mg to 0.468 mg, the maximum requirement occurring on day 2 of withdrawal and sinking thereafter. Since insomnia was not influenced by clonidine, we offered 100 mg doxepine and/or 10 mg nitrazepam (the latter only until day 4 of treatment). Under this medication a sudden, dramatic decrease in blood pressure was not seen, mean blood pressure and pulse rate were not markedly altered; this may, perhaps, be a consequence of the blocking effect of doxepine on the peripheral hypotensive actions of clonidine. Of the 9 drop-outs from treatment, five (10% of the total 50) were certainly directly attributable to the lack of response to clonidine, representing a failure of therapy in 10% cases at least.

[In-patient withdrawal treatment of heroin addicts with neuroleptics (author's transl)]. / Stationäre Entzugsbehandlung Heroinadhängiger mit Neuroleptika.

The results are reported of 144 abrupt withdrawal treatment in heroin addicts (102 in males, 42 in females). Neuroleptics were given intravenously (partly via subclavia catheter) or orally and the results compared with one another. Parenteral treatment needed much more specialist supervision and control and had a much higher complication rate. It should be used only on the individual special case. The initial withdrawal lasts about 4 days with an oral dosage of 270 mg levopromazine in males and 240 mg in females or 540 mg chlorprothixene in males and 520 mg in females per 24 hours. The only side effects encountered were tachycardia and the occasional occurrence of extrapyramidal signs. The liver function tests did not show any significant changes during the treatment.

[Connexions between instrumental delivery and cerebral damage in the infant (author's transl)]. / Zusammenhänge zwischen operativer Geburtsbeendigung und Zerebralschädigung des Kindes

An interdepartmental investigation was carried out on the incidence of brain injury, especially so-called minimal brain injury, after instrumental delivery of infants by means of forceps or vacuum extractor. There is no statistically-significant difference in the incidence of brain injury in infants delivered by means of forceps as compared with the vacuum extractor; there is, however, a significant increase in incidence of brain injury in infants following instrument-aided delivery as opposed to spontaneous delivery. A thorough explanation of the methods is given and the results are discussed.

[Nicotine--drug addiction--AIDS. Drug use habits of Vienna addicts]. / Nikotin--Drogensucht--AIDS. Drogengebrauchsgewohnheiten Wiener Süchtiger.

In Austria it is illegal to sell tobacco to young adolescents. A diverse sample of 358 narcotic addicts was investigated at the Psychiatric University Clinic of Vienna. Data were obtained from on site confidential interviews and a HIV-test was conducted. The individual drug use history was recorded and, interestingly, tobacco addiction was the first stage in starting a drug career. Furthermore, a strong correlation was observed between onset of heroin use and HIV-1 infection. It is concluded that in Austria not only the availability nicotine and alcohol to young adolescents should be prohibited, but also their use should be punishable. Easy access to nicotine as in public restaurants or from automatic distributors, has to be withdrawn. Tobacco advertisements may drive vulnerable young adolescents to early nicotine abuse and this may be followed by addition to other drugs and diseases causing death, including AIDS. Socioeconomic data, as well as the methadone data are presented. 180 out of the 358 patients were on methadone maintenance. Methadone treatment offers a first step toward social rehabilitation for drug addicts who have been living as criminals on the fringe of society. Physicians have a clear responsibility to lead the effort on all fronts against tobacco, especially in view of the HIV epidemic.

[Prevalence of HIV antibodies in intravenous drug-dependent patients 1986 and 1987 in Vienna]. / Die HIV-Antikörperprävalenz bei intravenös Drogenabhängigen 1986 und 1987 in Wien.

As one of the most important risk groups for HIV infection 82 intravenous drug addicts were tested in December 85/January 86 and 159 in December 86/January 87 for HIV antibody when entering a detoxification programme of our drug addition outpatient clinic. All these drug addicts had used intravenous drugs, mostly opiates. Serum antibodies to HIV were found in 7 (8.5%) of the first sample and in 23 (14.4%) of the second sample. Among seronegative drug addicts a significantly higher use of sterile needles was found than among HIV seropositive drug addicts. Among the seropositive drug abusers a history of intravenous drug abuse outside Austria was found more often than in seronegative drug addicts. The incidence of HIV antibodies in i.v. drug addicts in Vienna appears low in comparison with figures in the Austrian Tyrol (44%), Scotland (33%), Italy (53%) and Switzerland (53%), but similar to England (10%). The low frequency in Vienna could be explained by a significantly higher use of sterile equipment. Furthermore, at the first test period a change in abuse behaviour was found; an increasing number of patients was taking oral opiates exclusively, or reduced intravenous drug intake.

["Induced detoxification treatment" of opiate dependent patients--a new therapy concept]. / Die "induzierte Entzugsbehandlung" bei Opiatabhängigen--ein neues Therapiekonzept.

Induced detoxification treatment of opiate addicts by means of naloxone was developed at the intensive care unit of the Department of Psychiatry at the University of Vienna. Two methods were tested 1. Rapid opiate withdrawal by means of a staggered naloxone regimen. 2. Ultrashort opiate detoxification during general anaesthesia using high doses of naloxone. In an open trial 15 patients were treated with staggered doses of naloxone while under tiapride. The various discomforts were satisfactorily reduced, and the detoxification syndrome was limited to 50 hours. In a second open trial 6 patients were administered 10 mg naloxone under general anaesthesia. All naloxone induced withdrawal syndromes can be suppressed by barbiturate anaesthesia. They do not appear even after the effect of the anaesthesia wears off if the patient is kept on a naloxone regimen as long as opiates remain present in the circulatory system. Both methods shorten detoxification treatment and provide smooth transition to a naltrexone maintenance programme.

[Orally-administered taurine in therapy-resistant epilepsy (author's transl)]. / Orale Taurinmedikation bei therapieresistenten Epilepsien

The anticonvulsive action of taurine, was tested in 9 therapy in 9 therapy-resistant patients with a high incidence of seizures. Taurine was given orally (1.5-7.5 g daily) over a period of 4 to 16 weeks and, despite the high dosage, no appreciable side effects were observed. During this time seizures disappeared temporarily for about two weeks in 5 out of 9 cases. In one case the seizure frequency was transiently reduced by approximately 25%, whilst in the remaining 3 cases no effect of taurine on seizure frequency was observed. The reason for the rapid disappearance of the anticonvulsive action of taurine is not known.

[Initial clinical experiences in a large Austrian patient sample with immunodeficiency syndrome (AIDS): I. Type and course of encountered infections]. / Erste klinische Erfahrungen bei einem grösseren österreichischen Patientenkollektiv mit erworbenem Immunmangelsyndrom (AIDS): I. Art und Verlauf der aufgetretenen Infektionen.

This study presents a report on the first clinical experiences gained in 68 hospitalized HIV antibody-positive patients from Austria, covering a period of twelve months. 36 patients (52.9%) belonged to risk group I or Ib (homo- or bisexual), whereas 26 (38.2%) patients were i.v. drug abusers (risk group II). 5 (7.4%) patients fulfilled the criteria of stage II of the CDC classification of HIV-associated clinical symptoms, 10 (14.7%) were classified as stage III and the remaining 53 patients (78%) as stage IV. The most frequent and also the most serious problem was the development of opportunistic infections. Multiple infections were found in 45.7% of all cases. Kaposi's sarcoma was found in 9 patients who all belonged to risk group I. During the entire observation period 10 patients died as a consequence of HIV-1-induced immunodeficiency and the resulting opportunistic infections and/or neoplasms.

[Prevalence of HIV-1 infection in intravenous drug dependent patients 1986 to 1989 in Vienna]. / Prävalenz von HIV-1-Infektion bei intravenös Drogenabhängigen 1986 bis 1989 in Wien.

We report the results of a survey of a total of 553 intravenous drug users (IVDUs) investigated at the drug addiction out-patient unit of the Psychiatric Department of Vienna University for antibodies to human immunodeficiency virus (HIV-1) using both enzyme-linked immuno sorbent and Western blot assays. HIV-1 antibodies were found 1985/86 in 8.5%, 1986/87 in 14.5%, 1988 in 27.7% and 1989 in 29.7% of IVDUs. The introduction of methadone maintenance in 1987 attracted many IVDUs and increased the number of patients at the out-patient clinic. In 1989 more than 50% of the IVDUs are on methadone maintenance and already 84.5% of the HIV-1 infected drug users are treated with methadone.

[Maximal motor nerve conduction rate with lithium]. / Maximale motorische Nervenleitgeschwindigkeit unter Lithium.

We examined the nerve conduction velocity (NCV) of 10 patients under long-term lithium therapy and 10 patients after a 3-month lithium therapy. In accordance with the literature concerning patients and normals under experimental treatment with lithium, we also found reduced NCV values. There were no significant changes in NCV during the first 3 months of lithium treatment. This could be due to the relative low lithium levels as well as to symptoms of manic-depressive Illness and the nerve examined.